Warning: fopen(/home/virtual/enm-kes/journal/upload/ip_log/ip_log_2025-03.txt): failed to open stream: Permission denied in /home/virtual/lib/view_data.php on line 100 Warning: fwrite() expects parameter 1 to be resource, boolean given in /home/virtual/lib/view_data.php on line 101 Efficacy of Ethanol Ablation for Benign Thyroid Cysts and Predominantly Cystic Nodules: A Systematic Review and Meta-Analysis
Skip Navigation
Skip to contents

Endocrinol Metab : Endocrinology and Metabolism

clarivate
OPEN ACCESS
SEARCH
Search
Advanced Search
mobile menu button

Articles

Page Path
HOME > Endocrinol Metab > Volume 36(1); 2021 > Article
Original Article
Efficacy of Ethanol Ablation for Benign Thyroid Cysts and Predominantly Cystic Nodules: A Systematic Review and Meta-Analysis
Cheng-Chun Yangorcid, Yung Hsu, Jyun-Yan Liouorcid
Endocrinology and Metabolism 2021;36(1):81-95.
DOI: https://doi.org/10.3803/EnM.2020.833
Published online: February 24, 2021

Department of Medical Imaging, Chi Mei Medical Center, Tainan, Taiwan

Corresponding author: Jyun-Yan Liou. Division of Interventional Radiology, Department of Medical Imaging, Chi Mei Medical Center, No. 901, Zhonghua Rd., Yongkang Dist., Tainan 710, Taiwan, Tel: +886-6-281-2811, Fax: +886-6-622-2547, E-mail: wesbox@gmail.com
• Received: September 1, 2020   • Revised: November 10, 2020   • Accepted: December 10, 2020

Copyright © 2021 Korean Endocrine Society

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

  • 8,126 Views
  • 268 Download
  • 15 Web of Science
  • 19 Crossref
  • 22 Scopus
prev next
Full Article

Download PDF Download PDF

  • Background
    Ultrasound-guided minimally invasive procedures are widely used to treat thyroid diseases. The objective of this study was to assess the efficacy and safety of ethanol ablation (EA) in comparison with other non-surgical options in the treatment of benign thyroid cystic nodules.
  • Methods
    We conducted a systematic search of studies on EA for thyroid cystic nodules, mainly in the Ovid-MEDLINE and Embase, Web of Science, and Cochrane databases. The standardized mean difference (SMD) of the volume reduction ratio (VRR) after EA versus other non-surgical treatments comprised the primary outcome, whereas the odds ratio (OR) of therapeutic success rates between the two groups comprised the secondary outcome.
  • Results
    The meta-analysis included 19 studies (four randomized controlled trials and 15 non-randomized studies) with 1,514 participants. The cumulative VRR of EA was 83.908% (95% confidence interval [CI], 79.358% to 88.457%). EA had a significantly higher pooled VRR (SMD, 0.381; 95% CI, 0.028 to 0.734; P=0.030), but not a significantly higher pooled therapeutic success rate (OR, 0.867; 95% CI, 0.132 to 5.689; P=0.880), than other forms of non-surgical management including radiofrequency ablation (RFA), polidocanol sclerotherapy, and simple aspiration with or without saline flush. However, the VRR and therapeutic success rate were not significantly different between EA and RFA. Major complications were recorded only in six patients (0.53%) with self-limiting dysphonia.
  • Conclusion
    The role of EA as the first-line treatment for benign thyroid cysts and predominantly cystic nodules is supported by its high effectiveness and good safety profile compared to other currently available non-surgical options.
  • Keywords: Ethanol; Ablation techniques; Sclerotherapy; Thyroid nodule; Cyst; Meta-analysis
Thyroid nodules are very common incidental findings, detected in up to 67% of the general population by ultrasonography, and 15% to 25% of thyroid nodules are cystic [1,2]. Around 5% of patients with thyroid nodules may experience compressive symptoms or cosmetic concerns, and treatment may be required in these cases [3]. Simple aspiration is generally the initial management for the purpose of diagnosis and cyst volume reduction. However, the recurrence rate has been reported to be high (40% to 59%), depending on the number of aspirations and extent of fluid evacuation [4,5].
Ultrasound-guided percutaneous ethanol ablation (EA) is an effective and safe alternative to surgery in cases of recurrence. The reported volume reduction ratio (VRR) after EA in thyroid cysts (cystic portion >90%) and predominantly cystic thyroid nodules (PCTNs; typically defined as having a cystic portion of 50% to 90%) ranges from 80% to 100% and from 65% to 85.4%, respectively [6–13]. In contrast, the efficacy of EA for treating benign solid thyroid nodules remains controversial, and EA is not recommended in current guidelines for solid nodules [14]. The therapeutic mechanism of EA is a combination of coagulative and ischemic necrosis. The former is caused by direct ethanol toxicity leading to cell dehydration and protein denaturation, while the latter is induced by the entrance of ethanol into the local circulation, resulting in endothelial injury, subsequent thrombosis, and ischemia. Coagulative necrosis is considered to be the predominant effect on cystic lesions [15–17]. Although EA has been proposed as the first-line treatment for relapsing symptomatic cystic thyroid nodules in most guidelines [14,18–22], their recommendations point out a wide range of strengths based on previous reports with heterogeneous quality of evidence. The 2018 consensus statement on EA released by Korean Society of Thyroid Radiology accentuated the role of EA in treating benign thyroid cysts and PCTNs by summarizing more recent high-quality evidence, and further expanded its clinical scope for the management of hyperfunctioning thyroid nodules and local recurrent thyroid carcinoma in selected cases [22].
In recent years, thermal ablation has emerged as a popular non-surgical treatment for benign solid thyroid nodules and recurrent thyroid cancers [21]. In particular, radiofrequency ablation (RFA) has been shown to be effective for treating cystic thyroid nodules [8,10,13,23–26]. The objective of this study was to conduct a comprehensive meta-analysis to compare the efficacy and safety of EA with that of other non-surgical options, including RFA, for the treatment of benign thyroid cystic nodules.
Literature search
This meta-analysis adhered to the standard guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two reviewers (C.C.Y. and Y.H.) independently conducted a systematic search of the databases, including Ovid-MEDLINE and Embase, Web of Science, Cochrane Systematic Reviews, Cochrane Collaboration Central Register of Controlled Clinical Trials, ClinicalTrials.gov and Scopus. Additionally, major Korean medical databases including Korean Medical Article Database, KoreaMed.org, and KoreaMed Synapse were also searched, since most recent studies of EA are from Korea. The search strategy for Ovid-MEDLINE and Embase is presented in Supplemental Table S1. The search was updated to extend through October 2020.
Inclusion criteria
To conform to the population, intervention, comparison, and outcomes (PICO) strategy, our inclusion criteria were set as follows: (1) population: patients with thyroid cysts or PCTNs, for which benignity should be confirmed by fine-needle aspiration; (2) intervention and comparison: two-arm parallel studies comparing EA with other types of non-surgical management, and single-arm studies or case series involving EA with more than 10 participants; and (3) outcome: results reported in sufficient detail to evaluate the VRR (primary outcome, defined as: [final volume–baseline volume]/baseline volume), and therapeutic success rate (secondary outcome, defined as a volume reduction from baseline of more than 50%).
Exclusion criteria
Studies were excluded if any of the following criteria were met: (1) conference abstracts, letters, case series or case reports with fewer than 10 participants; (2) studies not written in English or for which the full text was not available; (3) studies with, or with suspicion of, overlapping populations; (4) studies that either had an arbitrary definition of benign thyroid cystic nodules, or did not enroll those with a cystic portion ≥50% of the nodule volume; and (5) studies that combined EA and other therapies as a whole.
Data extraction
One researcher (C.C.Y.) extracted the data from selected studies, while the other researcher (Y.H.) verified the accuracy. The following data was extracted with a standardized form: (1) mean VRR; (2) therapeutic success rate; (3) the types of nodules and their mean baseline volume; (4) patient demographics, including mean age and sex; (5) technical details, including the volume and concentration of injected ethanol, the retention and aspiration of injected ethanol, and number of treatment sessions; (6) timing of ultrasound follow-up; and (7) minor and major complications, categorized according to the new Society of Interventional Radiology classification [27]. Minor complications were defined as adverse events without requiring therapy, which were referred to as side effects in this study; major complications were defined as adverse events necessitating substantial therapy, escalation of care, hospitalization, life-threatening morbidity, or even mortality (Table 1).
Quality assessment
Two researchers independently assessed the quality of each included study with scoring systems corresponding to the research methodology. The Cochrane Risk-of-Bias tool 2.0 (RoB 2.0) contains five domains for the identification of potential source of bias in randomized controlled trials (RCTs): the randomization process, deviations from intended interventions, missing outcome data, the measurement of the outcomes, and selection of the reported results [28]. The Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS) evaluates the risk of bias in non-randomized studies (NRS) based on six domains: selection of participants, confounding variables, measurement of exposure, blinding of outcome assessment, incomplete outcome data, and selective outcome reporting [29]. Between-reviewer discrepancies were resolved through discussions under the supervision of the corresponding author.
Statistical synthesis and analysis
The standardized mean difference (SMD) of the VRR between EA and the control group comprised the primary outcome. A positive SMD indicates that EA was the favorable non-surgical treatment option. The effect size was analyzed in terms of the odds ratio (OR) for identifying the therapeutic success rate of EA. An OR >1 indicates that the EA group had a higher success rate than the control group. The inverse variance method and Mantel-Haenszel method were used to estimate the effect size of continuous and dichotomous variables, respectively. Additionally, the generic inverse variance method was employed to pool individual mean VRRs. A random-effects model was used to calculate each overall effect size. Sensitivity analyses, funnel plots and the Egger test were used to examine publication bias. A quantitative synthesis was done using the Cochrane Collaboration’s software RevMan 5.4, whereas the Egger test and sensitivity analyses were carried out using Comprehensive Meta-Analysis software version 3 (Biostat, Englewood, NJ, USA). Attempts were made to contact authors for missing data, and the remaining instances of missing data were dealt with reasonable imputation according to the Cochrane Handbook version 6. Between-trial heterogeneity was determined by the inconsistency index (I2), with values of 25%, 50%, and 75% representing low, moderate, and high degrees of inconsistency or statistical heterogeneity, respectively [30].
Literature search and characteristics of the included studies
A total of 1,772 non-duplicate potentially eligible studies were identified through screening the titles and abstracts, from which 46 articles were retrieved for full text review. The final meta-analysis included 19 studies, consisting of eight two-arm parallel studies (four RCTs [10,11,13,31], two prospective cohort studies [6,32], and two retrospective cohort studies [8,9]), which compared EA with other types of non-surgical management, and 11 single-arm studies (Fig. 1) [7,12,33–41]. Of note, Verde et al. [32] conducted a preliminary RCT followed by a prospective cohort, which was integrated into a larger cohort by pooling the VRRs at 1 month. The characteristics of the included studies are summarized in detail in Table 1.
Characteristics of the ablation techniques
Almost all EA procedures described in the included studies involved subtotal or complete aspiration of the fluid content of cystic nodules prior to ethanol instillation. The injected ethanol was either evacuated (aspiration technique) or retained (retention technique) after the procedure in seven [8–11,13,32,35] and three [31,40,41] studies, respectively. Notably, among studies that enrolled PCTNs, none of them mentioned injection of ethanol into the solid component in addition to filling of the cystic cavity. The procedure was well-tolerated by most participants, with no requirement for local anesthesia. Four trials evaluated the VRR after performing a single session of EA [10,13,32,35], whereas in the other studies, the VRR was assessed after some or all of the participants underwent multiple treatment sessions. The details of the EA techniques in the included studies are also presented in Table 1.
Assessment of study quality
The results of the quality assessment of the four included RCTs according to the RoB 2.0 tool are presented in Fig. 2A, Supplemental Fig. S1A. All four RCTs had a low risk of bias in the domains of deviations from intended interventions, missing outcome data, measurement of outcomes, and selection of the reported results. Three of the four studies were considered to have some concerns in the randomization process because the authors did not state allocation concealment [10,13,31], and one of them had a significant baseline imbalance in nodule volume and diameter [13]. The results of the methodological assessment of the 15 included NRSs according to the RoBANS are shown in Fig. 2B, Supplemental Fig. S1B. All the studies had a low risk of bias in the domain of selective outcome reporting, whereas most of them had an unclear risk of bias in the domain of blinding of outcome assessments. Six studies had a low risk of bias in the patient selection domain [6–9,35,38], while the others were given an unclear or high risk of bias due to an uncertain process of patient recruitment [12,33,39,41] and retrospective data collection [34,36,37,40] or selection of the intervention and control groups from different populations [32], respectively. One study had high risk of bias in the incomplete data domain due to a large number of dropout cases in long-term follow-up [7]. Additionally, one study had high and unclear risks of bias in the domains of confounding variables and measurement of exposure, respectively, because some of the patients in the control group received an additional suppressive dose of levothyroxine and the potential confounding effect on VRR was not investigated, and because it was not clearly described how exposure data were obtained [6].
Quantitative synthesis (meta-analysis)

Cumulative mean VRR of EA

The cumulative mean VRR of all the included 19 studies was 83.908% (95% confidence interval [CI], 79.358% to 88.457%), irrespective of the timing of ultrasound evaluation and number of treatment sessions. The pooled VRRs at 1, 6, and 12 months were 70.012% (95% CI, 62.620% to 77.404%), 90.754% (95% CI, 84.015% to 97.494%), and 84.966% (95% CI, 79.080% to 90.852%), respectively.

SMD of the VRR between EA and other types of non-surgical management

Overall, eight studies compared the VRR between EA and other non-surgical options [6,8–11,13,31,32]. The pooled SMD of EA versus other types of non-surgical management concerning VRR was 0.381 (95% CI, 0.028 to 0.734; P=0.030; I2=79%) (Fig. 3A). Subgroup analysis revealed no significant difference between VRR in the EA group and the RFA group (SMD, 0.170; 95% CI, −0.367 to 0.708; P=0.530; I2=61%), whereas the VRR of EA was significantly higher than that of simple aspiration with or without isotonic saline flush (SMD, 0.716; 95% CI, 0.292 to 1.140; P<0.001; I2=57%) (Fig. 3A). EA had a similar VRR to that of polidocanol sclerotherapy (SMD, −0.171; 95% CI, −0.410 to 0.068; P=0.160) (Fig. 3A). In the subgroup analysis of cysts versus PCTNs, one study [8] compared the two types of nodules separately and was therefore treated as containing two different datasets. Three studies were removed from consideration, including two [6,31] that combined the data of the different types of nodules, and another [32] that enrolled PCTNs with a different definition (cyst content >70%), because the authors believed that it was not reasonable to combine them into either group. Finally, we included six datasets from five studies for this subgroup analysis. As compared with other types of non-surgical management, the VRR after EA was higher in thyroid cysts (SMD, 0.333; 95% CI, −0.166 to 0.832; P=0.190; I2=76%) but not in PCTNs (SMD, −0.195; 95% CI, −0.495 to 0.104; P=0.200; I2=0%), although neither SMD achieved statistical significance (Fig. 3B). Table 2 presents the results of other subgroup analyses of SMDs based on study design, retention, and aspiration [42], injected ethanol volume, and the number of treatment sessions. Notably, in the subgroups of RCTs and studies that performed multiple treatment sessions, the SMDs of EA were significantly higher than those of the control treatments.

OR of the therapeutic success rate for EA and other types of non-surgical management

Among the eight included parallel studies, five trials [8–10,13, 32] were available for a quantitative analysis of the therapeutic success rate of EA and other non-surgical options. Of note, the therapeutic success rate was 100% in one arm of the study by Baek et al. [13], which was resolved by applying a continuity correction of 0.5 to each cell of the 2×2 table. However, one study was not included in the estimation of the pooled OR by default in the RevMan software because the therapeutic success rate was 100% in both arms [10], as such trials have a small effect on the pooled OR even when they comprise the large majority of included studies [43]. The pooled OR of the therapeutic success rates for EA as compared with other non-surgical managements was 0.867 (95% CI, 0.132 to 5.689; P=0.880; I2=75%) (Fig. 4A). A subgroup analysis showed no significant differences in the therapeutic success rate between EA and RFA (OR, 0.485; 95% CI, 0.071 to 3.328; P=0.460; I2=0%) (Fig. 4A). In the subgroup analysis of cysts versus PCTNs, the therapeutic success rate of EA was lower than the control types of management (RFA and polidocanol sclerotherapy) in both cysts and PCTNs ([OR, 0.488; 95% CI, 0.091 to 2.61; P=0.400; I2=0%] and [OR, 0.269; 95% CI, 0.079 to 0.921; P=0.040; I2=0%], respectively) (Fig. 4B).

Side effects and major complications

The most common side effect was mild to moderate local pain, which was transient and self-limiting in nearly all cases, without the need for analgesics. Drunkenness was reported to affect a small portion of the participants (10.4%) in one study [9]. Low-grade fever was a rare side effect documented by Valcavi and Frasoldati [31], which spontaneously resolved within 2 to 3 days without medication. Dysphonia was the major complication reported in eight patients from six studies [11,13,31, 34,38,40], with symptom duration ranging from a few minutes to 2 months. Two of the cases complicated by transient dysphonia reported by Guglielmi et al. [34] occurred in the other parallel group consisting of solid nodules, rather than the cystic nodules. Overall, the incidence of self-limiting dysphonia was 0.53% (six of the included 1,136 cases) in patients who underwent EA for benign thyroid cysts and PCTNs.
Sensitivity analysis and publication bias
In the sensitivity analysis (Supplemental Table S2), the quantitative syntheses were repeated after removing one study at a time. Although omitting individual trials did not change the direction of the relationship (favoring EA), the pooled SMD became statistically insignificant when four individual studies were removed, including most of the studies that compared EA with simple aspiration and saline instillation. The Egger test indicated no significant publication bias regarding the overall SMD (P=0.259). The funnel plot for the SMD of VRR is demonstrated in Fig. 5.
The present meta-analysis compared EA with other non-surgical types of management for the treatment of benign cystic thyroid nodules. Our results indicate that EA and RFA had comparable efficacy in treating cystic thyroid nodules with respect to VRR and the therapeutic success rate. This outcome is consistent with previous reports of high VRRs of RFA in both thyroid cysts and PCTNs (92.2%–93.3% and 83.7%–87.5%, respectively) [8,10, 13,44]. However, RFA is more expensive than EA and requires more treatment sessions to have an effect (1.67±0.86 vs. 1.19±0.4, P=0.03). It is also associated with a greater tendency for the patient to experience pain, both during and after the procedure [8,13]. In addition, EA appeared more effective in reducing the volume of thyroid cysts, but not PCTNs, albeit not to a statistically significant degree. These results correspond with the observation of a greater VRR in cysts than in PCTNs after EA from a previous study (89.7% vs. 78.2%, P<0.001) [45]. This can be explained by the conclusion of Kim et al. [12], who suggested that solid components of thyroid nodules are more refractory to EA based on their comparison of EA performed in cystic versus solid nodules. However, only one of the included studies compared EA with another form of sclerotherapy [9]. In fact, a variety of sclerosants in addition to ethanol have been adopted for the treatment of thyroid nodules, including tetracycline, sodium tetradecyl sulfate, N-butyl cyanoacrylate, and polidocanol [46–49]. Among them, polidocanol and sodium tetradecyl sulfate were compared with EA and were shown to have similar VRRs, but higher costs [9,47].
Several factors are known to compromise the efficacy of EA, particularly for PCTNs, including a relatively large initial nodule volume (>20 mL), increased vascularity, a solid portion >20% of the total nodule, and a relatively low degree of cystic fluid aspiration prior to ethanol instillation [35,45,50,51]. Technical factors have also been explored. Kim et al. [52] and Park et al. [42] compared retention and aspiration methods of the injected ethanol and found no significant difference between the two methods in terms of the therapeutic success rate and VRR, respectively. Similarly, different durations of temporary ethanol retention (i.e., 2, 5, and 10 minutes) did not significantly affect the VRR in a study assessing the treatment of cysts and PCTNs [45]. However, our subgroup analysis showed that only studies that performed the retention technique, rather than the aspiration technique, had significantly higher VRRs than other non-surgical options. Nonetheless, Kim et al. [12] demonstrated that a larger injected volume of ethanol was positively correlated with the VRR in thyroid cysts (P<0.01), but not in solid nodules. However, our subgroup analysis showed that EA achieved a significantly higher VRR in the group receiving a lower volume of ethanol instillation (<50% of the initial nodule volume), but not in the group with a higher injection volume. This is because patients in the control arm of the former group received conservative treatment (simple aspiration and saline flush) only. Moreover, the efficacy of EA is also influenced by the number of treatment sessions. Negro et al. [37] reported that the VRRs in thyroid cysts after the first, second, and third EA sessions were 66%, 74.4%, and 79.4%, respectively. Our subgroup analysis also showed that only studies that performed more than one session of EA in some or all of the patients demonstrated a significantly higher pooled VRR than the control management. Although the cure rate varied substantially across studies due to different definitions and numbers of interventions, Bennedbaek and Hegedus [11] reported a 64% cure rate (strictly defined as residual cyst volume ≤1 mL) after a single session of EA in thyroid cysts. Furthermore, the long-term efficacy of EA for cystic thyroid nodules is satisfactory, although long-term results were reported in just a few studies. The VRRs at 2, 3, 5, and 10 years of follow-up in different studies were 72.7%–91.9%, 73.2%–95.8%, 86.6%–98.5%, and 70.2%–100%, respectively [7,34,38,53,54]. The reported recurrence rates in thyroid cysts after EA were low (3.1%–18%), and also varied according to the criteria that were used [11,32,55]. However, in a more recent study of PCTNs, the 1-month recurrence rate was 18.7%, whereas delayed recurrence (mean, 10.1±8.5 months) occurred in 24.1% of patients who initially did not show recurrence at 1 month of follow-up [51]. When faced with unsatisfactory results after EA, current guidelines [19,21] recommend performing subsequent RFA based on previous studies reporting that significant reductions in nodule volume and improvements in symptomatic and cosmetic problems were achieved after this combination therapy [35,56]. Similarly, for incomplete ablation of solid nodules adjacent to critical structures after RFA, introducing EA as an adjunct technique was shown to be an effective way to eliminate the residual solid component [57,58].
EA is a safe procedure that is well-tolerated by most patients with benign thyroid cysts and PCTNs, with overall side effects that are mild and a considerably low incidence of major complications (self-limiting dysphonia, 0.53%). In contrast, dysphonia was reported in 15 of 1,459 patients (1.0%) who underwent RFA for benign thyroid nodules of unspecified morphological types in a large Korean multicenter study [59]. To our knowledge, permanent dysphonia after EA as a result of recurrent laryngeal nerve injury has never been reported, although severe necrosis of the skin and larynx without irreversible dysphonia was reported in one case involving treatment of a solid nodule [60]. Unlike with thermal ablation, the ablative effect of ethanol is limited to the nodule; therefore, EA does not disrupt thyroid function [6,32,39]. Moreover, local anesthesia was not required in most EA procedures. Notwithstanding its good safety profile, concerns can arise during the follow-up of patients treated with EA, as more than half of the remnant sclerosed nodules may mimic malignancy on ultrasound (i.e., marked hypoechogenicity), leading to unnecessary biopsies [61,62].
The present meta-analysis has some limitations. First, although several studies have assessed EA for the treatment of thyroid diseases, only a few trials have compared EA with other therapies. This fact limited the size of the current meta-analysis. Second, substantial heterogeneity was found with respect to the pooled VRR and therapeutic success rate of EA versus other non-surgical managements. We performed sensitivity analyses, and the pooled VRRs did not reach statistical significance if most studies involving conservative treatment as a comparator were omitted. Therefore, the results of this investigation should be interpreted with caution. More high-quality RCTs comparing EA with other minimally invasive procedures are needed. Third, changes in symptomatic and cosmetic parameters could not be pooled due to a lack of standardized effect size. However, they were shown to parallel the VRR in four included studies [8–10,13] performed using the same scales. Lastly, novel thermal ablative techniques using technologies such as microwave, laser, and high-intensity focused ultrasound have been implemented in recent years to treat thyroid disease. Future research should compare EA with these new treatment options.
In conclusion, EA achieved a higher pooled VRR than other types of non-surgical management and appears to be more effective in the treatment of thyroid cysts than PCTNs. Although RFA has a comparable level of effectiveness to EA, it is associated with higher expenses and greater technical complexity. Our results reinforce the role of EA as the first-line treatment for symptomatic thyroid cysts and PCTNs, given its high effectiveness, low-cost, and good safety profile.
Supplemental Table S1.
Search Strategy Used for Ovid-MEDLINE and Embase Databases
enm-2020-833-suppl1.pdf
Supplemental Table S2.
Sensitivity Analyses of the Effects of Individual Studies on the Pooled Standardized Mean Difference in the Volume Reduction Ratio
enm-2020-833-suppl2.pdf
Supplemental Fig. S1.
Quality assessment of the included randomized controlled trials according to Risk-of-Bias tool 2.0 (RoB 2.0) (A), and non-randomized studies according to Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS) (B).
enm-2020-833-suppl3.pdf
Acknowledgements
We are grateful to Dr. Chung-Han Ho for his help with the statistical analysis.

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

AUTHOR CONTRIBUTIONS

Conception or design: C.C.Y., Y.H., J.Y.L. Acquisition, analysis, or interpretation of data: C.C.Y., Y.H. Drafting the work or revising: C.C.Y., Y.H., J.Y.L. Final approval of the manuscript: C.C.Y., Y.H., J.Y.L.

Fig. 1
Flow diagram summarizing the literature review process according to the Preferred Reporting Items for Systemic Reviews and Meta-Analysis (PRISMA) guideline. VRR, volume reduction ratio; EA, ethanol ablation.
enm-2020-833f1.jpg
Fig. 2
Summary of quality assessment of the included randomized controlled trials according to Risk-of-Bias tool 2.0 (RoB 2.0) (A), and non-randomized studies according to Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS) (B).
enm-2020-833f2.jpg
Fig. 3
Forest plots summarizing the efficacy of ethanol ablation (EA) in treating cystic thyroid nodules measured by the volume reduction ratio as compared with other types of non-surgical management, overall effects, and subgroup analysis according to different comparators (A) and cysts versus predominantly cystic thyroid nodules (PCTNs) (B). SD, standard deviation; IV, inverse variance method; CI, confidence interval; RFA, radiofrequency ablation.
enm-2020-833f3.jpg
Fig. 4
Forest plots summarizing the therapeutic success rate of ethanol ablation (EA) as compared with other types of non-surgical management, overall effects, and subgroup analysis according to different comparators (A) and cysts versus predominantly cystic thyroid nodules (PCTNs) (B). M-H, Mantel-Haenszel; CI, confidence interval; RFA, radiofrequency ablation.
enm-2020-833f4.jpg
Fig. 5
Funnel plots of studies that evaluated the volume reduction ratio. SE, standard error; SMD, standardized mean difference; EA, ethanol ablation; RFA, radiofrequency ablation.
enm-2020-833f5.jpg
Table 1
Demographic Characteristics and Intervention Details of the Included Studies
Study Nodule type No. of cases (M/F) Control management Study design Mean age, yr Baseline nodule volume, mL EA technique Ultrasound evaluation, mo Side effects (n) Major complications (n)
Ethanol concentration, % Injection, % of cyst volume Retention, min Treatment sessions Local anesthesia
Sung et al. (2011) [8] Cyst EA: 36 (10/26)
Control: 21 (3/18)		 RFA RCS EA: 47.69±13.00
Control: 42.52±10.98		 EA: 12.2±11.0
Control: 9.3±11.7		 95–99 50 10 Multiple 2% lidocaine 1, 3, 6, 12, last f/ub Mild pain associated with needle puncture None
Sung et al. (2013) [10] Cyst EA: 25 (2/23)
Control: 25 (3/22)		 RFA RCT EA: 45.0±10.9
Control: 44.9±10.6		 EA: 13.83±11.97
Control: 10.19±7.01		 99 50 10 Single 2% lidocaine 1, 6b Almost no periprocedural pain None
Baek et al. (2015) [13] PCTN EA: 24 (6/18)
Control: 22 (3/19)		 RFA RCT EA: 50.8±15.2
Control: 49.8±13.5		 EA: 14.7±13.7
Control: 8.6±9.4		 99 50 2 Single 2% lidocaine 1, 6b None Voice change that spontaneously resolved 2 months later (1)
Gong et al. (2018) [9] Cyst, PCTN EA: 135 (50/85)
Control: 136 (56/80)		 Polidocanol sclerotherapy RCS EA: 46.83±11.31
Control: 49.52±11.53		 EA: 15.23±18.67
Control: 15.12±19.11		 NA 50 10 NA NA 1, 3, 6, 12b Mild to moderate pain lasting 1–5 days, drunkenness None
Verde et al. (1994) [32] Cystic nodulesa EA: 42
Control: 10		 Simple aspiration PCS NA EA: 20.10±15.40
Control: 26.24±11.37		 95 >70 5 Single None 1b, 12 Mild self- limiting pain None
Bennedbaek et al. (2003) [11] Cyst EA: 33 (4/29)
Control: 33 (7/26)		 Isotonic saline flush RCT EA: 48 (median)
Control: 46 (median)		 EA: 8.0±6.7
Control: 8.0±8.1		 99 36 2 Multiple None 1, 2, 3, 6b Transient pain Transient dysphonia lasting for 1 hour (1)
Valcavi et al. (2004) [31] Cyst, PCTN EA: 135
Control: 131		 Simple aspiration RCT NA EA: 19.0±19.0
Control: 20.0±13.4		 95–100 50–70 No withdrawal Multiple None 1, 2, 3, 6, 12b Transient burning sensation, late-onset Local tenderness (begins at 6–8 hours), low-grade fever (rare) Dysphonia that spontaneously resolved 2 months later (1)
Ferreira et al. (2016) [6] Cyst, PCTN EA: 36 (2/34)
Control: 13 (0/13)		 Conservative (f/u or other non-surgical treatments) PCS EA: 40.4±12.9
Control: 47±9.5		 EA: 10.4±9.8
Control: 6.2±3.1		 99 30 NA Multiple None 1 (mean), 14b (mean) Mild pain lingering for 3–4 days, edema None
Zingrillo et al. (1999) [7] Cyst 40 None BA NA 33.7±25.3 NA Variable NA Multiple NA 1, 6, 12, 24b, 36, 48, 60 Transient mild pain None
Cho et al. (2000) [33] Cystic nodulea 22 (4/18) None BA 40.7 13 NA 40–100 NA Multiple None 3.5b (mean) Local pain caused by leakage of ethanol into subcutaneous tissue (2) None
Kim et al. (2003) [12] Cystic nodulea 20 None BA NA 15.7 99.90 40–68 NA Multiple None 4.4b (mean) Transient pain caused by leakage of ethanol into subcutaneous tissue (4) None
Guglielmi et al. (2004) [34] Cystic nodulea 58 None BA NA 13.7±14.0 95 25 NA Multiple None 5b years None Transient dysphonia (2)c
Jang et al. (2012) [35] Cyst, PCTN 94 (21/73) EA+RFA BA 40.4 13.2±15.2 99 50 10 Single NA 1b Mild pain associated with needle removal None
Perez et al. (2014) [36] Cystic nodulea 14 None BA NA 12.2±12.3 99 33.3 NA Multiple None 6 months–11 years Transient pain caused by leakage of ethanol into subcutaneous tissue None
Reverter et al. (2015) [41] Cystic nodulea 30 (5/25) None BA 46±10 18.2±15.5 99 50 No withdrawal Multiple NA 12.1b (mean) Mild pain None
Negro et al. (2017) [37] Cyst 101 (30/71) None BA 42.3±12.9 14.8±15.5 Absolute ethanol NA NA Multiple Anesthetic sprayed locally ≤1b Transient mild to moderate pain (21.5%) None
Espenbetova et al. (2018) [38] Cystic nodulea 75 (3/72) None BA 57 (median) 18.4 95 70 NA Multiple 2% lidocaine 10±1.2b years Transient pain lasting for 1–2 days (1) Transient dysphonia (1)
Ozderya et al. (2018) [39] Cyst, PCTN 42 None BA NA 15.3±14.0 96 ≤20 NA Multiple None 1, 3, 6, 12b Transient mild pain at injection site None
Halenka et al. (2020) [40] Cystic nodulea 193 (43/150) None BA 49 8.5 (median) 96 Variable No withdrawal Multiple None 1, 3, 6, 12b Transient mild pain (29%), short- lasting dizziness Dysphonia spontaneously resolved within 14 days (2)

Values are expressed as mean±standard deviation.

EA, ethanol ablation; RFA, radiofrequency ablation; RCS, retrospective cohort study; f/u, follow-up; RCT, randomized controlled trial; PCTN, predominantly cystic thyroid nodule; PCS, prospective cohort study; NA, not available; BA, uncontrolled before-and-after comparison.

a Indicates different definitions of cystic nodules: Reverter et al. (cystic portion >80%); Verde et al. (cystic portion >70%); Cho et al., Kim et al, Espenbetova et al., Halenka et al. (cystic portion >60%); Perez et al. categorized nodules into cystic, mixed, and solid;

b Indicates the timing of outcome assessment;

c Indicates that the complication occurred in the parallel group consisting of solid nodules in the same study.

Table 2
Subgroup Analysis of Standardized Mean Difference Based on Study Design, Retention and Aspiration Techniques, and Injected Volume of Ethanol, and Number of Treatment Sessions
Subgroup Standardized mean difference 95% CI P value I2, %
Study design
 RCT 0.434 0.054 to 0.814 0.030 63
 NRS 0.364 −0.292 to 1.021 0.280 81
Retention and aspiration of injected ethanol
 Aspiration 0.384 −0.103 to 0.870 0.120 83
 Retention 0.407 0.164 to 0.650 0.001 NA
Injected volume
 ≥50% of cyst volume 0.300 −0.095 to 0.696 0.140 81
 <50% of cyst volume 0.751 0.295 to 1.207 0.001 0
Treatment session
 Single 0.605 −0.304 to 1.514 0.190 83
 Multiple 0.428 0.149 to 0.707 0.003 28

CI, confidence interval; RCT, randomized controlled trial; NRS, non-randomized study; NA, not applicable.

  • 1. Russ G, Leboulleux S, Leenhardt L, Hegedus L. Thyroid incidentalomas: epidemiology, risk stratification with ultrasound and workup. Eur Thyroid J 2014;3:154–63.ArticlePubMedPMC
  • 2. Rojeski MT, Gharib H. Nodular thyroid disease. Evaluation and management. N Engl J Med 1985;313:428–36.ArticlePubMed
  • 3. Durante C, Grani G, Lamartina L, Filetti S, Mandel SJ, Cooper DS. The diagnosis and management of thyroid nodules: a review. JAMA 2018;319:914–24.ArticlePubMed
  • 4. Smith MD, Serpell JW, Morgan JL, Cheng MS. Fine needle aspiration in the management of benign thyroid cysts. ANZ J Surg 2003;73:477–9.ArticlePubMed
  • 5. Choi WJ, Baek JH, Choi YJ, Lee JH, Ha EJ, Lee WC, et al. Management of cystic or predominantly cystic thyroid nodules: role of simple aspiration of internal fluid. Endocr Res 2015;40:215–9.ArticlePubMed
  • 6. Ferreira MC, Piaia C, Cadore AC. Percutaneous ethanol injection versus conservative treatment for benign cystic and mixed thyroid nodules. Arch Endocrinol Metab 2016;60:211–6.ArticlePubMedPMC
  • 7. Zingrillo M, Torlontano M, Chiarella R, Ghiggi MR, Nirchio V, Bisceglia M, et al. Percutaneous ethanol injection may be a definitive treatment for symptomatic thyroid cystic nodules not treatable by surgery: five-year follow-up study. Thyroid 1999;9:763–7.ArticlePubMed
  • 8. Sung JY, Kim YS, Choi H, Lee JH, Baek JH. Optimum first-line treatment technique for benign cystic thyroid nodules: ethanol ablation or radiofrequency ablation? AJR Am J Roentgenol 2011;196:W210–4.ArticlePubMed
  • 9. Gong X, Wang F, Du H, Chen X, Shi B. Comparison of ultrasound-guided percutaneous polidocanol injection versus percutaneous ethanol injection for treatment of benign cystic thyroid nodules. J Ultrasound Med 2018;37:1423–9.ArticlePubMed
  • 10. Sung JY, Baek JH, Kim KS, Lee D, Yoo H, Kim JK, et al. Single-session treatment of benign cystic thyroid nodules with ethanol versus radiofrequency ablation: a prospective randomized study. Radiology 2013;269:293–300.ArticlePubMed
  • 11. Bennedbaek FN, Hegedus L. Treatment of recurrent thyroid cysts with ethanol: a randomized double-blind controlled trial. J Clin Endocrinol Metab 2003;88:5773–7.ArticlePubMed
  • 12. Kim JH, Lee HK, Lee JH, Ahn IM, Choi CG. Efficacy of sonographically guided percutaneous ethanol injection for treatment of thyroid cysts versus solid thyroid nodules. AJR Am J Roentgenol 2003;180:1723–6.ArticlePubMed
  • 13. Baek JH, Ha EJ, Choi YJ, Sung JY, Kim JK, Shong YK. Radiofrequency versus ethanol ablation for treating predominantly cystic thyroid nodules: a randomized clinical trial. Korean J Radiol 2015;16:1332–40.ArticlePubMedPMC
  • 14. Gharib H, Papini E, Garber JR, Duick DS, Harrell RM, Hegedus L, et al. American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules: 2016 update. Endocr Pract 2016;22:622–39.PubMed
  • 15. Shiina S, Tagawa K, Unuma T, Takanashi R, Yoshiura K, Komatsu Y, et al. Percutaneous ethanol injection therapy for hepatocellular carcinoma. A histopathologic study. Cancer 1991;68:1524–30.ArticlePubMed
  • 16. Albanese G, Kondo KL. Pharmacology of sclerotherapy. Semin Intervent Radiol 2010;27:391–9.ArticlePubMedPMC
  • 17. Ahmed M, Brace CL, Lee FT Jr, Goldberg SN. Principles of and advances in percutaneous ablation. Radiology 2011;258:351–69.ArticlePubMedPMC
  • 18. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association Guidelines Task Force on thyroid nodules and differentiated thyroid cancer. Thyroid 2016;26:1–133.ArticlePubMedPMC
  • 19. Papini E, Monpeyssen H, Frasoldati A, Hegedus L. 2020 European Thyroid Association clinical practice guideline for the use of image-guided ablation in benign thyroid nodules. Eur Thyroid J 2020;9:172–85.ArticlePubMedPMC
  • 20. Feldkamp J, Grunwald F, Luster M, Lorenz K, Vorlander C, Fuhrer D. Non-surgical and non-radioiodine techniques for ablation of benign thyroid nodules: consensus statement and recommendation. Exp Clin Endocrinol Diabetes 2020;128:687–92.ArticlePubMed
  • 21. Kim JH, Baek JH, Lim HK, Ahn HS, Baek SM, Choi YJ, et al. 2017 Thyroid radiofrequency ablation guideline: Korean Society of Thyroid Radiology. Korean J Radiol 2018;19:632–55.ArticlePubMedPMC
  • 22. Hahn SY, Shin JH, Na DG, Ha EJ, Ahn HS, Lim HK, et al. Ethanol ablation of the thyroid nodules: 2018 consensus statement by the Korean Society of Thyroid Radiology. Korean J Radiol 2019;20:609–20.ArticlePubMedPMC
  • 23. Jeong WK, Baek JH, Rhim H, Kim YS, Kwak MS, Jeong HJ, et al. Radiofrequency ablation of benign thyroid nodules: safety and imaging follow-up in 236 patients. Eur Radiol 2008;18:1244–50.ArticlePubMed
  • 24. Lim HK, Lee JH, Ha EJ, Sung JY, Kim JK, Baek JH. Radiofrequency ablation of benign non-functioning thyroid nodules: 4-year follow-up results for 111 patients. Eur Radiol 2013;23:1044–9.ArticlePubMed
  • 25. Aysan E, Idiz UO, Akbulut H, Elmas L. Single-session radiofrequency ablation on benign thyroid nodules: a prospective single center study : radiofrequency ablation on thyroid. Langenbecks Arch Surg 2016;401:357–63.ArticlePubMed
  • 26. Kim YS, Rhim H, Tae K, Park DW, Kim ST. Radiofrequency ablation of benign cold thyroid nodules: initial clinical experience. Thyroid 2006;16:361–7.ArticlePubMed
  • 27. Khalilzadeh O, Baerlocher MO, Shyn PB, Connolly BL, Devane AM, Morris CS, et al. Proposal of a new adverse event classification by the Society of Interventional Radiology Standards of Practice Committee. J Vasc Interv Radiol 2017;28:1432–7.ArticlePubMed
  • 28. Sterne JAC, Savovic J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019;366:l4898.ArticlePubMed
  • 29. Kim SY, Park JE, Lee YJ, Seo HJ, Sheen SS, Hahn S, et al. Testing a tool for assessing the risk of bias for nonrandomized studies showed moderate reliability and promising validity. J Clin Epidemiol 2013;66:408–14.ArticlePubMed
  • 30. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557–60.ArticlePubMedPMC
  • 31. Valcavi R, Frasoldati A. Ultrasound-guided percutaneous ethanol injection therapy in thyroid cystic nodules. Endocr Pract 2004;10:269–75.ArticlePubMed
  • 32. Verde G, Papini E, Pacella CM, Gallotti C, Delpiano S, Strada S, et al. Ultrasound guided percutaneous ethanol injection in the treatment of cystic thyroid nodules. Clin Endocrinol (Oxf) 1994;41:719–24.ArticlePubMed
  • 33. Cho YS, Lee HK, Ahn IM, Lim SM, Kim DH, Choi CG, et al. Sonographically guided ethanol sclerotherapy for benign thyroid cysts: results in 22 patients. AJR Am J Roentgenol 2000;174:213–6.PubMed
  • 34. Guglielmi R, Pacella CM, Bianchini A, Bizzarri G, Rinaldi R, Graziano FM, et al. Percutaneous ethanol injection treatment in benign thyroid lesions: role and efficacy. Thyroid 2004;14:125–31.ArticlePubMed
  • 35. Jang SW, Baek JH, Kim JK, Sung JY, Choi H, Lim HK, et al. How to manage the patients with unsatisfactory results after ethanol ablation for thyroid nodules: role of radiofrequency ablation. Eur J Radiol 2012;81:905–10.ArticlePubMed
  • 36. Perez CL, Fighera TM, Miasaki F, Mesa Junior CO, Paz Filho GJ, Graf H, et al. Evaluation of percutaneous ethanol injections in benign thyroid nodules. Arq Bras Endocrinol Metabol 2014;58:912–7.ArticlePubMed
  • 37. Negro R, Colosimo E, Greco G. Outcome, pain perception, and health-related quality of life in patients submitted to percutaneous ethanol injection for simple thyroid cysts. J Thyroid Res 2017 2017:9536479.Article
  • 38. Espenbetova M, Amrenova K, Zhumanbayeva Z, Zamanbekova Z, Yurkovskaya O, Shalgumbayeva G, et al. Effectiveness of percutaneous ethanol injection in nodular diseases of the thyroid gland: 10-year follow-up. Endoc Pract 2018;24:982–7.Article
  • 39. Ozderya A, Aydin K, Gokkaya N, Temizkan S. Percutaneous ethanol injection for benign cystic and mixed thyroid nodules. Endocr Pract 2018;24:548–55.ArticlePubMed
  • 40. Halenka M, Karasek D, Schovanek J, Frysak Z. Safe and effective percutaneous ethanol injection therapy of 200 thyroid cysts. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2020;164:161–7.ArticlePubMed
  • 41. Reverter JL, Alonso N, Avila M, Lucas A, Mauricio D, Puig-Domingo M. Evaluation of efficacy, safety, pain perception and health-related quality of life of percutaneous ethanol injection as first-line treatment in symptomatic thyroid cysts. BMC Endocr Disord 2015;15:73.ArticlePubMedPMC
  • 42. Park HS, Yim Y, Baek JH, Choi YJ, Shong YK, Lee JH. Ethanol ablation as a treatment strategy for benign cystic thyroid nodules: a comparison of the ethanol retention and aspiration techniques. Ultrasonography 2019;38:166–71.ArticlePubMed
  • 43. Friedrich JO, Adhikari NK, Beyene J. Inclusion of zero total event trials in meta-analyses maintains analytic consistency and incorporates all available data. BMC Med Res Methodol 2007;7:5.ArticlePubMedPMC
  • 44. Lee GM, You JY, Kim HY, Chai YJ, Kim HK, Dionigi G, et al. Successful radiofrequency ablation strategies for benign thyroid nodules. Endocrine 2019;64:316–21.ArticlePubMed
  • 45. Kim YJ, Baek JH, Ha EJ, Lim HK, Lee JH, Sung JY, et al. Cystic versus predominantly cystic thyroid nodules: efficacy of ethanol ablation and analysis of related factors. Eur Radiol 2012;22:1573–8.ArticlePubMed
  • 46. Hegedus L, Hansen JM, Karstrup S, Torp-Pedersen S, Juul N. Tetracycline for sclerosis of thyroid cysts. A randomized study. Arch Intern Med 1988;148:1116–8.ArticlePubMed
  • 47. Kalra N, Ahuja CK, Dutta P, Rajwanshi A, Mittal BR, Bhansali A, et al. Comparison of sonographically guided percutaneous sodium tetradecyl sulfate injection with ethanol injection in the treatment of benign nonfunctioning thyroid nodules. J Vasc Interv Radiol 2014;25:1218–24.ArticlePubMed
  • 48. Dong Y, Zhou J, Liu Z, Luo T, Zhan W. Efficacy assessment of ultrasound guided lauromacrogol injection for ablation of benign cystic and predominantly cystic thyroid nodules. Front Pharmacol 2019;10:478.ArticlePubMedPMC
  • 49. Yuce G, Ates OF, Polat B, Genc B, Canyigit M. Ablation of cystic thyroid nodules with n-butyl cyanoacrylate: a preliminary study. Endocr Pract 2020;26:492–8.ArticlePubMed
  • 50. In HS, Kim DW, Choo HJ, Jung SJ, Kang T, Ryu JH. Ethanol ablation of benign thyroid cysts and predominantly cystic thyroid nodules: factors that predict outcome. Endocrine 2014;46:107–13.ArticlePubMed
  • 51. Suh CH, Baek JH, Ha EJ, Choi YJ, Lee JH, Kim JK, et al. Ethanol ablation of predominantly cystic thyroid nodules: evaluation of recurrence rate and factors related to recurrence. Clin Radiol 2015;70:42–7.ArticlePubMed
  • 52. Kim DW, Rho MH, Kim HJ, Kwon JS, Sung YS, Lee SW. Percutaneous ethanol injection for benign cystic thyroid nodules: is aspiration of ethanol-mixed fluid advantageous? AJNR Am J Neuroradiol 2005;26:2122–7.PubMedPMC
  • 53. Lee SJ, Ahn IM. Effectiveness of percutaneous ethanol injection therapy in benign nodular and cystic thyroid diseases: long-term follow-up experience. Endocr J 2005;52:455–62.ArticlePubMed
  • 54. Solymosi T. Percutaneous ethanol injection efficacy in the treatment of benign thyroid nodules. Ten-year follow-up of 254 patients. Orv Hetil 2020;161:224–31.PubMed
  • 55. Monzani F, Lippi F, Goletti O, Del Guerra P, Caraccio N, Lippolis PV, et al. Percutaneous aspiration and ethanol sclerotherapy for thyroid cysts. J Clin Endocrinol Metab 1994;78:800–2.ArticlePubMed
  • 56. Lee JH, Kim YS, Lee D, Choi H, Yoo H, Baek JH. Radiofrequency ablation (RFA) of benign thyroid nodules in patients with incompletely resolved clinical problems after ethanol ablation (EA). World J Surg 2010;34:1488–93.ArticlePubMed
  • 57. Kim DW. Sonography-guided ethanol ablation of a remnant solid component after radio-frequency ablation of benign solid thyroid nodules: a preliminary study. AJNR Am J Neuroradiol 2012;33:1139–43.ArticlePubMedPMC
  • 58. Park HS, Baek JH, Choi YJ, Lee JH. Innovative techniques for image-guided ablation of benign thyroid nodules: combined ethanol and radiofrequency ablation. Korean J Radiol 2017;18:461–9.ArticlePubMedPMC
  • 59. Baek JH, Lee JH, Sung JY, Bae JI, Kim KT, Sim J, et al. Complications encountered in the treatment of benign thyroid nodules with US-guided radiofrequency ablation: a multicenter study. Radiology 2012;262:335–42.ArticlePubMed
  • 60. Mauz PS, Maassen MM, Braun B, Brosch S. How safe is percutaneous ethanol injection for treatment of thyroid nodule? Report of a case of severe toxic necrosis of the larynx and adjacent skin. Acta Otolaryngol 2004;124:1226–30.ArticlePubMed
  • 61. Park NH, Kim DW, Park HJ, Lee EJ, Park JS, Park SI, et al. Thyroid cysts treated with ethanol ablation can mimic malignancy during sonographic follow-up. J Clin Ultrasound 2011;39:441–6.ArticlePubMed
  • 62. Park JS, Kim DW, Eun CK, Choi SJ, Rho MH. Long-term follow-up sonography of benign cystic thyroid nodules after a percutaneous ethanol injection: the incidence of malignancy-mimicking nodules. J Korean Radiol Soc 2008;58:21–8.Article

Figure & Data

References

    Citations

    Citations to this article as recorded by  
    • Ultrasound-guided ethanol ablation versus the Sistrunk operation as a primary treatment for thyroglossal duct cysts
      Dongbin Ahn, Ji Hye Kwak, Gil Joon Lee, Jin Ho Sohn
      Ultrasonography.2024; 43(1): 25.     CrossRef
    • The Comparison of Efficacy and Safety between Radiofrequency Ablation Alone and Ethanol Ablation Followed by Radiofrequency Ablation in the Treatment of Mixed Cystic and Solid Thyroid Nodule
      Min Gang Jo, Min Kyoung Lee, Jae Ho Shin, Min Guk Seo, So Lyung Jung
      Journal of the Korean Society of Radiology.2024; 85(3): 618.     CrossRef
    • Prevalence and Management of Complications of Percutaneous Ethanol Injection for Cystic Thyroid Nodules: A Systematic Review of Literature and Meta-analysis
      Lorenzo Scappaticcio, Pamela Ferrazzano, Nicole Di Martino, Roberto Negro, Maurilio Deandrea, Maria Ida Maiorino, Paola Caruso, Michela Di Nuzzo, Miriam Longo, Giovanni Docimo, Giampaolo Papi, Pierpaolo Trimboli, Katherine Esposito, Giuseppe Bellastella
      Thyroid®.2024; 34(9): 1068.     CrossRef
    • Current role of interventional radiology in thyroid nodules
      Onur Taydas, Erbil Arik, Omer Faruk Sevinc, Ahmet Burak Kara, Mustafa Ozdemir, Hasret Cengiz, Zulfu Bayhan, Mehmet Halil Ozturk
      Frontiers in Endocrinology.2024;[Epub]     CrossRef
    • Ethanol Ablation Is a Safe Treatment Option for Cystic and Predominantly Cystic Thyroid Nodules
      Iram Hussain
      Clinical Thyroidology®.2024; 36(11): 412.     CrossRef
    • Percutaneous Ethanol Sclerotherapy for Head-and-Neck Lymphatic Malformation: A Systematic Review and Case Report
      Xin Ler Pang, Stephanie He Shengjie, Man Hon Tang, Joel Lau Wen Liang, Wei Keat Cheah, Yi-Xiu Chua, Hui Seong Teh, Si Zhao Tang
      Journal of Endocrine Surgery.2024; 24(4): 119.     CrossRef
    • Ultrasound-Guided Ethanol Ablation for Thyroglossal Duct Cyst: A Review of Technical Issues and Potential as a New Standard Treatment
      Dongbin Ahn
      Journal of Clinical Medicine.2023; 12(17): 5445.     CrossRef
    • Ultrasound‐Guided Ethanol Ablation as a Primary Treatment for Thyroglossal Duct Cyst: Feasibility, Characteristics, and Outcomes
      Dongbin Ahn, Ji Hye Kwak, Gil Joon Lee, Jin Ho Sohn
      Otolaryngology–Head and Neck Surgery.2023; 168(6): 1381.     CrossRef
    • Ultraschallgeführte lokalablative Verfahren zur Behandlung von Schilddrüsenläsionen
      Johannes-Paul Richter, Carl-Philip Richter, Daniel Gröner
      Angewandte Nuklearmedizin.2023; 46(02): 169.     CrossRef
    • A Case of Thyroid Abscess Following Ethanol Ablation for Benign Thyroid Nodule
      Heungrae Cho, Dongbin Ahn, Ji Hye Kwak, Gil Joon Lee
      Korean Journal of Otorhinolaryngology-Head and Neck Surgery.2023; 66(9): 624.     CrossRef
    • Sclerotherapy with a Viscum Album Extract for the Two Patients with Cystic Thyroid Nodule
      Jae Ha Lee, Seung Won Lee, Ki Nam Park
      International Journal of Thyroidology.2023; 16(1): 139.     CrossRef
    • Percutaneous ethanol injection in thyroid nodular pathology and metastatic cervical adenopathies: A systematic review, meta-analysis and economic evaluation
      Beatriz León-Salas, Aránzazu Hernández-Yumar, Diego Infante-Ventura, Aythami de Armas Castellano, Yadira González Hernández, Renata Linertová, Teresa Téllez Santana, Pedro de Pablos-Velasco, María M. Trujillo-Martín
      Endocrinología, Diabetes y Nutrición.2023; 70(9): 572.     CrossRef
    • Ultraschallgeführte lokalablative Verfahren zur Behandlung von Schilddrüsenläsionen
      Johannes-Paul Richter, Carl-Philip Richter, Daniel Gröner
      Laryngo-Rhino-Otologie.2023; 102(12): 916.     CrossRef
    • Percutaneous ethanol injection in thyroid nodular pathology and metastatic cervical adenopathies: A systematic review, meta-analysis and economic evaluation
      Beatriz León-Salas, Aránzazu Hernández-Yumar, Diego Infante-Ventura, Aythami de Armas Castellano, Yadira González Hernández, Renata Linertová, Teresa Téllez Santana, Pedro de Pablos-Velasco, María M. Trujillo-Martín
      Endocrinología, Diabetes y Nutrición (English ed.).2023; 70(9): 572.     CrossRef
    • Safety and Efficacy of Ultrasound-Guided Radiofrequency Ablation for Benign Nonfunctional Thyroid Nodules in Children: A Retrospective Study of 62 Patients with Over Four Years of Follow-Up
      Liwen Li, Xinguang Qiu
      Thyroid.2022; 32(5): 525.     CrossRef
    • Ethanol ablation for the treatment of benign thyroid nodules
      Gabrielle K. Steinl, Latoya A. Stewart, Catherine McManus, James A. Lee, Jennifer H. Kuo
      The American Journal of Surgery.2022; 224(1): 408.     CrossRef
    • Minimally-invasive treatments for benign thyroid nodules: recommendations for information to patients and referring physicians by the Italian Minimally-Invasive Treatments of the Thyroid group
      Giovanni Mauri, Stella Bernardi, Andrea Palermo, Roberto Cesareo, Enrico Papini, Luigi Solbiati, Daniele Barbaro, Salvatore Monti, Maurilio Deandrea, Laura Fugazzola, Giovanni Gambelunghe, Roberto Negro, Stefano Spiezia, Fulvio Stacul, Luca Maria Sconfien
      Endocrine.2022; 76(1): 1.     CrossRef
    • Image-Guided Percutaneous Ablation for Primary and Metastatic Tumors
      Arian Mansur, Tushar Garg, Apurva Shrigiriwar, Vahid Etezadi, Christos Georgiades, Peiman Habibollahi, Timothy C. Huber, Juan C. Camacho, Sherif G. Nour, Alan Alper Sag, John David Prologo, Nariman Nezami
      Diagnostics.2022; 12(6): 1300.     CrossRef
    • Approach to FNA of Thyroid Gland Cysts
      Esther Diana Rossi, Pietro Tralongo, Vincenzo Fiorentino, Mariangela Curatolo, Carmine Bruno, Carmen De Crea, Marco Raffaelli, Alfredo Pontecorvi, Luigi Maria Larocca
      Advances in Anatomic Pathology.2022; 29(6): 358.     CrossRef

    Figure
    • 0
    • 1
    • 2
    • 3
    • 4
    Related articles
    Efficacy of Ethanol Ablation for Benign Thyroid Cysts and Predominantly Cystic Nodules: A Systematic Review and Meta-Analysis
    Image Image Image Image Image
    Fig. 1 Flow diagram summarizing the literature review process according to the Preferred Reporting Items for Systemic Reviews and Meta-Analysis (PRISMA) guideline. VRR, volume reduction ratio; EA, ethanol ablation.
    Fig. 2 Summary of quality assessment of the included randomized controlled trials according to Risk-of-Bias tool 2.0 (RoB 2.0) (A), and non-randomized studies according to Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS) (B).
    Fig. 3 Forest plots summarizing the efficacy of ethanol ablation (EA) in treating cystic thyroid nodules measured by the volume reduction ratio as compared with other types of non-surgical management, overall effects, and subgroup analysis according to different comparators (A) and cysts versus predominantly cystic thyroid nodules (PCTNs) (B). SD, standard deviation; IV, inverse variance method; CI, confidence interval; RFA, radiofrequency ablation.
    Fig. 4 Forest plots summarizing the therapeutic success rate of ethanol ablation (EA) as compared with other types of non-surgical management, overall effects, and subgroup analysis according to different comparators (A) and cysts versus predominantly cystic thyroid nodules (PCTNs) (B). M-H, Mantel-Haenszel; CI, confidence interval; RFA, radiofrequency ablation.
    Fig. 5 Funnel plots of studies that evaluated the volume reduction ratio. SE, standard error; SMD, standardized mean difference; EA, ethanol ablation; RFA, radiofrequency ablation.

    Fig. 1

    Fig. 2

    Fig. 3

    Fig. 4

    Fig. 5

    Efficacy of Ethanol Ablation for Benign Thyroid Cysts and Predominantly Cystic Nodules: A Systematic Review and Meta-Analysis
    Study Nodule type No. of cases (M/F) Control management Study design Mean age, yr Baseline nodule volume, mL EA technique Ultrasound evaluation, mo Side effects (n) Major complications (n)
    Ethanol concentration, % Injection, % of cyst volume Retention, min Treatment sessions Local anesthesia
    Sung et al. (2011) [8] Cyst EA: 36 (10/26)
    Control: 21 (3/18)    		 RFA RCS EA: 47.69±13.00
    Control: 42.52±10.98    		 EA: 12.2±11.0
    Control: 9.3±11.7    		 95–99 50 10 Multiple 2% lidocaine 1, 3, 6, 12, last f/ub Mild pain associated with needle puncture None
    Sung et al. (2013) [10] Cyst EA: 25 (2/23)
    Control: 25 (3/22)    		 RFA RCT EA: 45.0±10.9
    Control: 44.9±10.6    		 EA: 13.83±11.97
    Control: 10.19±7.01    		 99 50 10 Single 2% lidocaine 1, 6b Almost no periprocedural pain None
    Baek et al. (2015) [13] PCTN EA: 24 (6/18)
    Control: 22 (3/19)    		 RFA RCT EA: 50.8±15.2
    Control: 49.8±13.5    		 EA: 14.7±13.7
    Control: 8.6±9.4    		 99 50 2 Single 2% lidocaine 1, 6b None Voice change that spontaneously resolved 2 months later (1)
    Gong et al. (2018) [9] Cyst, PCTN EA: 135 (50/85)
    Control: 136 (56/80)    		 Polidocanol sclerotherapy RCS EA: 46.83±11.31
    Control: 49.52±11.53    		 EA: 15.23±18.67
    Control: 15.12±19.11    		 NA 50 10 NA NA 1, 3, 6, 12b Mild to moderate pain lasting 1–5 days, drunkenness None
    Verde et al. (1994) [32] Cystic nodulesa EA: 42
    Control: 10    		 Simple aspiration PCS NA EA: 20.10±15.40
    Control: 26.24±11.37    		 95 >70 5 Single None 1b, 12 Mild self- limiting pain None
    Bennedbaek et al. (2003) [11] Cyst EA: 33 (4/29)
    Control: 33 (7/26)    		 Isotonic saline flush RCT EA: 48 (median)
    Control: 46 (median)    		 EA: 8.0±6.7
    Control: 8.0±8.1    		 99 36 2 Multiple None 1, 2, 3, 6b Transient pain Transient dysphonia lasting for 1 hour (1)
    Valcavi et al. (2004) [31] Cyst, PCTN EA: 135
    Control: 131    		 Simple aspiration RCT NA EA: 19.0±19.0
    Control: 20.0±13.4    		 95–100 50–70 No withdrawal Multiple None 1, 2, 3, 6, 12b Transient burning sensation, late-onset Local tenderness (begins at 6–8 hours), low-grade fever (rare) Dysphonia that spontaneously resolved 2 months later (1)
    Ferreira et al. (2016) [6] Cyst, PCTN EA: 36 (2/34)
    Control: 13 (0/13)    		 Conservative (f/u or other non-surgical treatments) PCS EA: 40.4±12.9
    Control: 47±9.5    		 EA: 10.4±9.8
    Control: 6.2±3.1    		 99 30 NA Multiple None 1 (mean), 14b (mean) Mild pain lingering for 3–4 days, edema None
    Zingrillo et al. (1999) [7] Cyst 40 None BA NA 33.7±25.3 NA Variable NA Multiple NA 1, 6, 12, 24b, 36, 48, 60 Transient mild pain None
    Cho et al. (2000) [33] Cystic nodulea 22 (4/18) None BA 40.7 13 NA 40–100 NA Multiple None 3.5b (mean) Local pain caused by leakage of ethanol into subcutaneous tissue (2) None
    Kim et al. (2003) [12] Cystic nodulea 20 None BA NA 15.7 99.90 40–68 NA Multiple None 4.4b (mean) Transient pain caused by leakage of ethanol into subcutaneous tissue (4) None
    Guglielmi et al. (2004) [34] Cystic nodulea 58 None BA NA 13.7±14.0 95 25 NA Multiple None 5b years None Transient dysphonia (2)c
    Jang et al. (2012) [35] Cyst, PCTN 94 (21/73) EA+RFA BA 40.4 13.2±15.2 99 50 10 Single NA 1b Mild pain associated with needle removal None
    Perez et al. (2014) [36] Cystic nodulea 14 None BA NA 12.2±12.3 99 33.3 NA Multiple None 6 months–11 years Transient pain caused by leakage of ethanol into subcutaneous tissue None
    Reverter et al. (2015) [41] Cystic nodulea 30 (5/25) None BA 46±10 18.2±15.5 99 50 No withdrawal Multiple NA 12.1b (mean) Mild pain None
    Negro et al. (2017) [37] Cyst 101 (30/71) None BA 42.3±12.9 14.8±15.5 Absolute ethanol NA NA Multiple Anesthetic sprayed locally ≤1b Transient mild to moderate pain (21.5%) None
    Espenbetova et al. (2018) [38] Cystic nodulea 75 (3/72) None BA 57 (median) 18.4 95 70 NA Multiple 2% lidocaine 10±1.2b years Transient pain lasting for 1–2 days (1) Transient dysphonia (1)
    Ozderya et al. (2018) [39] Cyst, PCTN 42 None BA NA 15.3±14.0 96 ≤20 NA Multiple None 1, 3, 6, 12b Transient mild pain at injection site None
    Halenka et al. (2020) [40] Cystic nodulea 193 (43/150) None BA 49 8.5 (median) 96 Variable No withdrawal Multiple None 1, 3, 6, 12b Transient mild pain (29%), short- lasting dizziness Dysphonia spontaneously resolved within 14 days (2)
    Subgroup Standardized mean difference 95% CI P value I2, %
    Study design
     RCT 0.434 0.054 to 0.814 0.030 63
     NRS 0.364 −0.292 to 1.021 0.280 81
    Retention and aspiration of injected ethanol
     Aspiration 0.384 −0.103 to 0.870 0.120 83
     Retention 0.407 0.164 to 0.650 0.001 NA
    Injected volume
     ≥50% of cyst volume 0.300 −0.095 to 0.696 0.140 81
     <50% of cyst volume 0.751 0.295 to 1.207 0.001 0
    Treatment session
     Single 0.605 −0.304 to 1.514 0.190 83
     Multiple 0.428 0.149 to 0.707 0.003 28
    Table 1 Demographic Characteristics and Intervention Details of the Included Studies

    Values are expressed as mean±standard deviation.

    EA, ethanol ablation; RFA, radiofrequency ablation; RCS, retrospective cohort study; f/u, follow-up; RCT, randomized controlled trial; PCTN, predominantly cystic thyroid nodule; PCS, prospective cohort study; NA, not available; BA, uncontrolled before-and-after comparison.

    Indicates different definitions of cystic nodules: Reverter et al. (cystic portion >80%); Verde et al. (cystic portion >70%); Cho et al., Kim et al, Espenbetova et al., Halenka et al. (cystic portion >60%); Perez et al. categorized nodules into cystic, mixed, and solid;

    Indicates the timing of outcome assessment;

    Indicates that the complication occurred in the parallel group consisting of solid nodules in the same study.

    Table 2 Subgroup Analysis of Standardized Mean Difference Based on Study Design, Retention and Aspiration Techniques, and Injected Volume of Ethanol, and Number of Treatment Sessions

    CI, confidence interval; RCT, randomized controlled trial; NRS, non-randomized study; NA, not applicable.

    Table 1

    Table 2

    Endocrinol Metab : Endocrinology and Metabolism
    © Korean Endocrine Society.
    TOP